Author:
Raj Desh,Nair Abhilash Vijay,Sharma Jyotsna,Prakash Shakti,Kaushik Aman,Basu Swarnali,Sahu Shikha,Singh Shriya,Bhosale Vivek,Chandra Tulika,Ghoshal Uday C,Dasgupta Arunava,Siddiqi Mohammad Imran,Gupta Shashi Kumar,Chakravortty Dipshikha,Ammanathan Veena,Lahiri Amit
Abstract
AbstractIntracellularSalmonellaresides and multiplies in cholesterol-rich specialized compartment calledSalmonella-containing vacuoles (SCVs) and avoids fusion with acidic lysosomes. Given, lysosomes are primary organelle that redistributes LDL derived cholesterol to other organelles; we questioned how lysosomal cholesterol can be transported to SCV. We demonstrate here that peroxisomes are recruited to SCVs in human primary macrophages, epithelial cells and functions as pro-bacterial organelles. Further, this interaction is assisted by SseI, aSalmonellaeffector protein containing mammalian peroxisome targeting sequence. SseI localizes to peroxisome, interacts and activates a host Ras GTPase, ARF-1 on the peroxisome membrane. Activation of ARF-1 leads to recruitment of phosphatidylinsolitol-5- phosphate-4 kinase to generate phosphatidylinsolitol-4-5-bisphosphate on peroxisomes. Accordingly, theΔsseIstrain showed reduced virulence in cell lines and during mice infection. Taken together, our work identified a fascinating mechanism by which a pathogen targets host organelles via its secretory effectors and exploits host metabolic intermediates for its intracellular proliferation.
Publisher
Cold Spring Harbor Laboratory